Relay Therapeutics, Inc. · NASDAQ:RLAY
Relay Therapeutics — Investor Day (June 2022)
50 slides from Relay Therapeutics's investor day presentation, Jun 27, 2022
Slide 1: Analyst & Investor Event June 27, 2022
Analyst & Investor Event June 27, 2022 Exhibit 99.2
Slide 2: Disclaimer
Disclaimer This presentation contains forward-looking statements and information about our current and future prospects and our operations and financial results, which are based on currently available information. All statements other than statements of historical facts contained in this presentatio
Slide 3: Relay Tx – Patient-Driven & Execution Focused
Relay Tx – Patient-Driven & Execution Focused Clear Focus Validated Targets Therapeutic Areas Modalities Small molecules Oncology Genetic diseases Challengers Innovators Validated Approach PI3KαPAN RLY-2608 FGFR2 RLY-4008 PI3KαPAN RLY-5836 Execution-Focused Selective CDK2 SHP2 RLY-1971 ERα Degrader
Slide 4: 2022 Commitments & Disclosures to be Made Today
2022 Commitments & Disclosures to be Made Today RLY-2608 (PI3KαPAN) RLY-4008 (FGFR2) Next target in pipeline RLY-1971 (SHP2) Selective CDK2 inhibitor Expansion cohorts open Additional data update in 2H 2022 Clinical trial initiated GDC-6036 (KRAS G12C) combination trial initiated in July 2021 ERα de
Slide 5: Agenda
Future Guidance and Q&A 4 Agenda Overview of DynamoTM Platform 3 Breast Cancer Portfolio 2 RLY-4008 Regulatory Update 1
Slide 6: RLY-4008: FGFR2 Selective Inhibitor – Alignment on Registrational Trial Design
RLY-4008: FGFR2 Selective Inhibitor – Alignment on Registrational Trial Design Preliminary data as of 19-April-2022 Potential for RLY-4008 as an important treatment option for patients Alignment with FDA on single arm, trial design for FGFRi-naïve FGFR2-fusion CCA to potentially support accelerated
Slide 7: Relay Tx’s Emerging Breast Cancer Franchise
Relay Tx’s Emerging Breast Cancer Franchise *Covers H1047X, E542X, E545X hot spots 2 Relay Tx’s PI3Kα Franchise PI3KαPAN PI3KαSPECIFIC PI3KαOTHER RLY-2608* Pan-mutant selective allosteric inhibitor H1047R-specific allosteric inhibitor Other mutant-selective mechanisms Additional chemically distinct
Slide 8: Relay Tx – Understanding Next Generation Drug Discovery: Questions
Relay Tx – Understanding Next Generation Drug Discovery: 4 Questions EXPERIMENTATION COMPUTATION PEOPLE Modulation Hypothesis Hit Identification Lead Optimization The “How” How do we work to solve problems? The “What” What problems do we work on? The “Where” Where do we focus? The Impact How do we m
Slide 9: Relay Tx – Capital, Team & Execution Focus to Deliver on Anticipated Milestones
Relay Tx – Capital, Team & Execution Focus to Deliver on Anticipated Milestones 4 RLY-4008 (Selective FGFR2) Clinical start in Q4 2023 or Q1 2024 Selective CDK2 RLY-1971 (SHP2) Atezolizumab combo trial to be initiated in 2H 2022 RLY-2608 (PI3KαPAN) $898M Cash, cash equivalents and investments as of
Slide 10: Agenda
Future Guidance and Q&A 4 Agenda Overview of DynamoTM Platform 3 Breast Cancer Portfolio 2 RLY-4008 Regulatory Update 1
Slide 11: RLY-4008 – Context: October 2021 Clinical Data Disclosure - Dose Escalation
RLY-4008 – Context: October 2021 Clinical Data Disclosure - Dose Escalation Source: RLY-4008 data as presented at 2021 AACR-NCI-EORTC Molecular Targets Conference Data from 2021 AACR-NCI-EORTC Molecule Targets Presentation (October 2021, n = 49 patients) Execution 49 patients (through October 2021)
Slide 12: RLY-4008 - Dose Escalation: BID De-Prioritized & 70 mg QD Selected
RLY-4008 - Dose Escalation BID Schedule De-Prioritized & 70 mg QD Selected For Expansion Cohorts Data from 2021 AACR NCI-EOR TC Molecule Targets Presentation (October 2021) FGFR2 - RLY-4008 FIH Study: Parallel Bayesian Dose Optimization Ongoing Dose cohort enrollment periods - Bayesian dose optimiza
Slide 13: RLY-4008 – Continued Clinical Execution
RLY-4008 – Continued Clinical Execution Presentation at EORTC NCI AACR in Oct 2021 (as of 9 Sept 2021) Total Total QD (once daily) 70 mg QD Total Patients Dosed 49 115 58 11 Cholangiocarcinoma (CCA) Patients FGFRi pre-treated Fusion 25 49 25 1 Other FGFR2 alteration 3 6 2 1 FGFRi naïve Fusion 7* 24
Slide 14: RLY-4008 – Treatment Emergent Adverse Events Profile
RLY-4008 – Treatment Emergent Adverse Events (TEAEs) Profile TEAEs >20% Preliminary data as of 19-April-2022 Note: Treatment-emergent adverse events (TEAEs) ≥ 20% in total population Median time on treatment (wks) 16 18 16 Dose modification due to related TEAEs Dose interruption (%) 38 38 55 Dose re
Slide 15: RLY-4008 – Radiographic Tumor Regression in FGFRi-Naïve Cholangiocarcinoma
RLY-4008 – Radiographic Tumor Regression Data Continue to Show Promise for FGFRi-Naïve Cholangiocarcinoma QD Patients Preliminary data as of 19-April-2022 In October 2021 disclosure: 3 out of 6 fusion+ CCA FGFRi naïve patients with confirmed PRs In June 2022 disclosure: 8/13 pts with confirmed PRs,
Slide 16: RLY-4008 – Time on Treatment for FGFRi-Naïve Cholangiocarcinoma QD Patients
RLY-4008 – Time on Treatment for FGFRi-Naïve Cholangiocarcinoma QD Patients 35-year old patient currently ongoing on adjuvant therapy with RLY-4008 (sIND) after complete resection with curative intent, no evidence of disease as of 31 May 2022 Preliminary data as of 19-April-2022 5/8 responders remai
Slide 17: RLY-4008 - Patient with Near Complete Regression of FGFR2-Fusion CCA
Treatment with RLY-4008 RLY-4008 - Patient with Near Complete Regression of FGFR2-Fusion, FGFRi-Naïve CCA Underwent Resection with No Evidence of Disease as of May 2022 Preliminary data as of May 2022 Treatment with RLY-4008 (70 mg QD) First Dose Mar 2021 Resection Sept 2021 Single Patient IND Dec 2
Slide 18: RLY-4008 – Pivotal Study Design
RLY-4008 – Pivotal Study Design FGFR2-fusion+ cholangiocarcinoma (CCA) without prior FGFRi (n=100) FGFR2-fusion+ CCA with prior FGFRi (n=50) FGFR2-fusion+ CCA with no prior treatment (n=20) Any FGFR2-mutant/amplified CCA (n=20) Pivotal Expansion Supportive cohorts Pivotal cohort FGFR2-fusion+ cholan
Slide 19: RLY-4008 – Exemplary Clinical Execution
RLY-4008 – Exemplary Clinical Execution Completed extensive dose exploration Continued promising safety and tolerability profile Signs of promising efficacy Defined regulatory plan Twice Daily (BID) n = 17 Intermittent n = 40 100 mg 50 mg 30 mg 20 mg Once Daily (QD) n = 58 115 patients enrolled acro
Slide 20: Agenda
Future Guidance and Q&A 4 Agenda Overview of DynamoTM Platform 3 Breast Cancer Portfolio 2 RLY-4008 Regulatory Update 1
Slide 21: Breast Cancer – Challenges with Current Treatment Landscape
Breast Cancer – Challenges with Current Treatment Landscape ET - Endocrine Therapy 1Adjuvant treatment outcome sources: SEER; van de Velde 2011 Lancet 377:321; Morden 2017 J Clin Oncol 35:2507; Jakesz 2005 Lancet 366:455; Margolese 2016 Lancet 387:849; Blok 2017 J Natl Cancer Inst 1:110; Anastrozole
Slide 22: Relay Tx’s Emerging Breast Cancer Franchise
Relay Tx’s Emerging Breast Cancer Franchise *Covers H1047X, E542X, E545X hot spots Relay Tx’s PI3Kα Franchise PI3KαPAN PI3KαSPECIFIC PI3KαOTHER RLY-2608* Pan-mutant selective allosteric inhibitor H1047R-specific allosteric inhibitor Other mutant-selective mechanisms Additional chemically distinct pr
Slide 23: Seeking to Transform the Breast Cancer Treatment Paradigm
Seeking to Transform the Breast Cancer Treatment Paradigm Potential near-term augmentation of standard of care* Aspirational future standard of care First Line Second and Third Line Multiple ETs CDK 4/6s Alt. ET Adjuvant Multiple ETs CDK 4/6 Alpelisib Chemo Alt. CDK4/6 RLY-2608 RLY-2608 RLY-2608 Sel
Slide 24: PI3Kα – RLY-2608 Trial Design
PI3Kα – RLY-2608 Trial Design Part 1: Dose Escalation a. Excludes PIK3CAmut clear cell OvCA (ovarian cancer), HNSCC (head & neck squamous cell carcinoma), and Cervical cancer patients; b. Double mutation defined as one major PIK3CA mutation (E542X, E545X, H1047X) + ≥1 additional PI3KCA mutation per
Slide 25: Relay Tx’s Emerging Breast Cancer Franchise
Relay Tx’s Emerging Breast Cancer Franchise *Covers H1047X, E542X, E545X hot spots Relay Tx’s PI3Kα Franchise PI3KαPAN PI3KαSPECIFIC PI3KαOTHER RLY-2608* Pan-mutant selective allosteric inhibitor H1047R-specific allosteric inhibitor Other mutant-selective mechanisms Additional chemically distinct pr
Slide 26: Relay Tx’s Emerging Breast Cancer Franchise
Relay Tx’s Emerging Breast Cancer Franchise *Covers H1047X, E542X, E545X hot spots Relay Tx’s PI3Kα Franchise PI3KαPAN PI3KαSPECIFIC PI3KαOTHER RLY-2608* Pan-mutant selective allosteric inhibitor H1047R-specific allosteric inhibitor Other mutant-selective mechanisms Additional chemically distinct pr
Slide 27: CDK2 – A Validated Target in ER+ Breast Cancer
CDK2 – A Validated Target in ER+ Breast Cancer Cyclin E activates CDK2 to drive cancer Clinical data demonstrate the importance of CDK2 in ER+ breast cancer Turner, N.C., et al. JCO 2019 Higher CDK2 activity associated with worse response to CDK4/6 inhibition Growth phase 1 DNA replication Growth ph
Slide 28: CDK2 – Unlocking Insights Into the Drivers of CDK2 Selectivity
CDK2 – Relay Tx Unlocking Insights Into the Drivers of CDK2 Selectivity Relay Tx Approach Motion-based insights into drivers of CDK2 selectivity… …leveraged to design highly selective CDK2 inhibitors Traditional approach Non-selective CDK inhibitors
Slide 29: CDK2 – Computational Modeling Designed to Enable Breakthrough Speed
CDK2 – Computational Modeling Designed to Enable Breakthrough Speed Collect MD frames 500 frames / MD 1000’s of MDs Extract features ~50,000 distances / frame Cluster frames 100 clusters / CDK Assign cluster populations 200 cl. pops / ligand Predict selectivity Clusters Compounds First compound synt
Slide 30: CDK2 – Highly Selective Inhibitors with Combination Potential with RLY-2608
CDK2 – Relay Tx’s CDK2 Inhibitors Observed to be Highly Selective and Demonstrated Combination Potential with RLY-2608 in Breast Cancer RTX-1 and RTX-2 achieved exquisite selectivity for a CDK2 inhibitor Clinical start expected in Q4 2023 or Q1 2024 RTX-2 was synergistic with RLY-2608 (PI3KαPAN) in
Slide 31: Relay Tx’s Emerging Breast Cancer Franchise
Relay Tx’s Emerging Breast Cancer Franchise *Covers H1047X, E542X, E545X hot spots Relay Tx’s PI3Kα Franchise PI3KαPAN PI3KαSPECIFIC PI3KαOTHER RLY-2608* Pan-mutant selective allosteric inhibitor H1047R-specific allosteric inhibitor Other mutant-selective mechanisms Additional chemically distinct pr
Slide 32: ERα Degrader – Endocrine Therapy is Central in HR+/HER2- Breast Cancer
ERα Degrader – Endocrine Therapy is Central in the Treatment of HR+/HER2- Breast Cancer Endocrine therapies are currently used in every line of therapy in HR+/HER2- Breast Cancer Enabling degradation of the estrogen receptor (ER) protein E3 E2 Ub ER protein E3 Ligase System This enables degradation
Slide 33: ERα Degrader – Rational Design of Targeted Protein Degraders
ERα Degrader – Rational Design of Targeted Protein Degraders Multiple experimental tools deployed…. …to inform long-time scale MD models X-ray Crystallography Cryo-EM Conformational models enable effective triage of degrader design ideas Traditional Approach Relay Tx Approach Binary complex HDX-MS
Slide 34: ERα Degrader – Rapidly Obtained Potent Degraders of ERα
ERα Degrader – Relay Tx has Rapidly Obtained Potent Degraders of ERα Protein degradation* Cellular proliferation* Cellular degradation kinetics ERa protein levels 20 0 -20 -40 -60 -80 -100 -12 -10 -8 -6 -4 Compound concentration Cell survival 20 0 -20 -40 -60 -80 -100 -12 -10 -8 -6 -4 Compound conce
Slide 35: Large Breast Cancer Patient Population
Large Breast Cancer Patient Population Relay Tx’s PI3Kα Franchise PI3KαPAN PI3KαSPECIFIC PI3KαOTHER RLY-2608* Pan-mutant selective allosteric inhibitor H1047R-specific allosteric inhibitor Other mutant-selective mechanisms Additional chemically distinct programs Relay Tx Rational Combination Partner
Slide 36: Agenda
Future Guidance and Q&A 4 Agenda Overview of DynamoTM Platform 3 Breast Cancer Portfolio 2 RLY-4008 Regulatory Update 1
Slide 37: Relay Tx – Understanding Next Generation Drug Discovery: Questions
Relay Tx – Understanding Next Generation Drug Discovery: 4 Questions EXPERIMENTATION COMPUTATION PEOPLE Modulation Hypothesis Hit Identification Lead Optimization The “How” How do we work to solve problems? The “What” What problems do we work on? The “Where” Where do we focus? The Impact How do we m
Slide 38: Relay Tx – Where We Focus Our Dynamo Platform Today
Commercial-ization Relay Tx – Where We Focus Our Dynamo™ Platform Today Development “Where?” Understand how to drug the protein Modulation Hypothesis Hit Identification Lead Optimization Identify a chemical starting point Optimize until development candidate selected Target Identification
Slide 39: Relay Tx – What Problems We Tackle
Commercial-ization Relay Tx – What Problems We Tackle Development Lead Optimization Hit Identification Modulation Hypothesis Target is known driver of disease Amenable to Dynamo platform Clear patient selection strategy Anticipated rapid path to clinical POC “What?” Unvalidated Targets Validated Tar
Slide 40: Relay Tx – How Our Team Solves Problems – The Dynamo Platform
Relay Tx – How Our Team Solves Problems – The Dynamo™ Platform Chemical biology insights Deep structural understanding Physics-based simulations AI / ML PEOPLE EXPERIMENTATION COMPUTATION “How?”
Slide 41: Relay Tx – Our 3-Step Drug Discovery Process
Relay Tx – How Our Team Solves Problems – Our 3-Step Drug Discovery Process Chemical biology insights Deep structural understanding Physics-based simulations AI / ML PEOPLE EXPERIMENTATION COMPUTATION Experimental tool examples: Computational tool examples: Lead Optimization Oral Administration Hit
Slide 42: Relay Tx – Using Industry-Leading Expertise
Relay Tx – How Our Team Solves Problems – Using Industry-Leading Expertise We believe the Relay Tx Team is leading the field of Automated Chemical Design (ACD) ACD Framework describes automated small molecule design systems “How?”
Slide 43: Relay Tx – Measuring our Impact
Multiple Relay Tx – Measuring our Impact RLY-4008 (Selective FGFR2) RLY-2608 (PI3KαPAN) RLY-1971 (SHP2) RLY-5836 (PI3KαPAN) Selective CDK2 Pre-Clinical POC1 DC Selection2 First Patient Dosed Early Clinical Validation Approval ERα Degrader Pivotal Initiation Impact 1POC - proof-of-concept. 2DC - deve
Slide 44: Relay Tx – Understanding Next Generation Drug Discovery: Questions
Relay Tx – Understanding Next Generation Drug Discovery: 4 Questions EXPERIMENTATION COMPUTATION PEOPLE Modulation Hypothesis Hit Identification Lead Optimization The “How” How do we work to solve problems? The “What” What problems do we work on? The “Where” Where do we focus? The Impact How do we m
Slide 45: Agenda
Future Guidance and Q&A 4 Agenda Overview of DynamoTM Platform 3 Breast Cancer Portfolio 2 RLY-4008 Regulatory Update 1
Slide 46: 2022 Milestones – Proven Execution Focus
2022 Milestones – Proven Execution Focus RLY-2608 (PI3KαPAN) RLY-4008 (FGFR2) Next target in pipeline RLY-1971 (SHP2) Selective CDK2 Expansion cohorts open Additional data update in 2H 2022 Clinical trial initiated GDC-6036 (KRAS G12C) combination trial initiated in July 2021 ERα Degrader Regulatory
Slide 47: Relay Tx – Extensive Precision Medicine Focused Pipeline
Breast Cancer1 PI3Kα franchise PI3KαPAN RLY-26082 RLY-2608 Pan-mutant allosteric inhibitor ~8-51K ~50-156K all solid tumors RLY-58362 PI3KαSPECIFIC H1047R-specific RLY-1047R H1047R allosteric inhibitor ~4-25K ~15-48K all solid tumors PI3KαOTHER Additional Other novel mutant selective mechanisms To b
Slide 48: Relay Tx – Capital, Team & Execution Focus to Deliver on Anticipated Milestones
Relay Tx – Capital, Team & Execution Focus to Deliver on Anticipated Milestones RLY-4008 (Selective FGFR2) Selective CDK2 RLY-1971 (SHP2) RLY-2608 (PI3KαPAN) $898M Cash, cash equivalents and investments as of the end of Q1 2022 ERα Degrader Tumor Agnostic Breast Cancer Franchise Current cash, cash e
Slide 49: Q&A
Q&A
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